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Introduction: Liposomes have been extensively investigated as drug delivery vehicles. Immunoliposomes (ILs) are antibody-conjugated liposomes designed to selectively target antigen-expressing cells. ILs can be used to deliver drugs to tumor cells for improving efficacy and reducing toxicity. In addition, ILs can be used in immunoassays, immunotherapy, and imaging. Although there has been extensive coverage on ILs in the literature, only a limited number of clinical trials have been reported and no IL drug has been approved by the FDA.

Areas covered: Factors to consider in developing ILs are discussed, including the choice of antibody or antibody fragment, the formulation of liposomes, and the conjugation chemistry. In addition, challenges and opportunities in clinical development of ILs are discussed. The purpose of this review is to provide an overview on the state of the art of ILs and to discuss potential future developments.

Expert opinion: IL research has had a lengthy history and numerous preclinical studies have yielded encouraging results. However, there are a number of obstacles to clinical translation of ILs. Given the unique capabilities of ILs, its potential for clinical application is underexplored. There is great potential for expanded role for ILs in the clinic and further efforts to this end are warranted.

Abbreviations: Ab: antibody; ADCs: antibody-drug conjugates; API: active pharmaceutical ingredient; ADCC: antibody-dependent cellular cytotoxicity; CR: complete remission; cGMP: current good manufacturing practice; DSPE: distearoyl phosphatidylethanolamine; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPR: enhanced permeability and retention; Fc: fragment crystalline; Tf: transferrin; HACA: human-anti-chimeric antibody; HAHA: human-anti-human antibody; HAMA: human-anti-mouse antibody; HER2: human epidermal growth factor 2; IL: immunoliposome; LNPs: lipid nanoparticles; MRI: magnetic resonance imaging; MTD: maximum tolerated dose; PEG: polyethylene glycol; PET: positron emission tomography; PR: partial response; PSMA: prostate-specific membrane antigen; scFv: single-chain variable fragment; SPECT: single photon emission computed tomography; TTR: transthyretin  相似文献   

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To identify an agent with specific activity against B-lineage leukaemia stem cells (B-LSCs), we generated norcantharidin (NCTD)-encapsulated liposomes modified with a novel humanised anti-human CD19 monoclonal antibody, Hm2E8b (Hm2E8b–NCTD–liposomes). These liposomes were specially designed to recognise and kill B-LSCs in vitro, and to decrease non-specific cytotoxicity to untargeted cells. Hm2E8b–NCTD–liposomes selectively ablated B-LSCs through targeting hepatic leukaemia factor (HLF), which is implicated in haematopoietic stem cell regulation and is overexpressed in LSCs. Hm2E8b–NCTD–liposomes decreased HLF protein levels and induced apoptosis in the HAL-01 cell line harbouring the oncoprotein E2A–HLF. This resulted in modulation of the expression of several molecules that govern survival pathways, including HLF, SLUG, NFIL3 and C-Myc, thereby causing the induction of p53 and the mitochondrial caspase cascade. Therefore, the potent in vitro effect of Hm2E8b–NCTD–liposomes on B-LSC activity and survival pathways have the potential to be exploited clinically with appropriate drug combinations.  相似文献   
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A novel immunoliposome delivery system was developed for directed transport into cultured olfactory epithelium cells. Monoclonal antibodies against glial fibrillary acidic protein (GFAP) served as a vector. Fluorescence microscopy showed that the target cells are specifically stained with Dil dye incorporated into liposomal membranes. This transport system holds promise for the delivery of bioactive substances to olfactory epithelial cells and modulation of their capacity to stimulate axonal regeneration. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 427–430, April, 2008  相似文献   
5.
大肠癌特异性卡莫氟免疫脂质体的体外抗癌活性研究   总被引:3,自引:0,他引:3  
目的研制抗人体大肠癌的单克隆抗体的卡莫氟免疫脂质体 ,并对其体外抗癌活性进行了研究。方法由偶联剂将抗大肠癌的单抗与载药脂质体偶联制成免疫脂质体 ,并应用酶联免疫吸附法和MTT法分别测定其免疫活性和体外细胞毒毒性。结果脂质体稳定性良好 ,制成免疫脂质体后 ,单抗免疫活性不丧失 ;体外细胞毒实验结果显示 ,卡莫氟免疫脂质体对人大肠癌细胞的体外抗癌活性优于普通脂质体和游离药物 ,IC50 分别为两者的 1 0 6和 3 5 9倍 ,对非靶细胞的作用与普通脂质体相似。结论卡莫氟免疫脂质体对细胞生长的抑制作用有明显的靶向特异性  相似文献   
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目的:构建靶向EGFR的光敏脂质体,提高化疗药物对胃癌细胞系的杀伤效果,并降低相关毒副反应。方法:以联乙炔基甘油磷脂酰胆碱(Diacetylenic glycerophosphatidylcholine,PC)(以下简称PC)为原料,采用薄膜分散法制备光反应性脂质体,表面修饰表皮生长因子受体(Epidermal growth factor receptor,EGFR)抗体Certuximab的Fab’片段,交联脂质体,制备靶向光敏脂质体,增强其在肿瘤组织内部的富集以及肿瘤细胞对脂质体药物的摄取。透射电镜观察脂质体的形态,动态光散射仪测定脂质体的粒径和血液学稳定性,倒置荧光显微镜和流式细胞术检测人体胃腺癌细胞N87对脂质体药物的摄取能力,CCK-8试剂盒(Cell Counting Kit-8)比较脂质体与游离药物对人体胃癌细胞N87细胞的体外杀伤效应,荷瘤小鼠皮下肿瘤抑制实验比较脂质体药物与游离药物对N87细胞的体内杀伤效应。结果:制备出的对紫外线敏感的EGFR靶向脂质体具有规整的球状结构、合适的粒径大小和很强的血液学稳定性。胃癌细胞N87对靶向脂质体(PC-Dox-Fab,PDF)的摄取能力较非靶向脂质体(PC-Dox-BSA,PDB)和游离DOX有显著增强(P<0.05)。PDF对N87细胞的半数抑制浓度(Half inhibitory concentration,IC50)较PDB及游离DOX有显著降低(P<0.05)。体内研究结果显示,PDF能够显著抑制荷瘤小鼠的皮下肿瘤生长(P<0.05)。结论:本研究制备的靶向EGFR的光敏脂质体拥有很好的稳定性,在体内外研究中对胃癌细胞具有很强的杀伤效果,具有广阔的临床应用前景。  相似文献   
7.
免疫脂质体是用抗体或其片段修饰的脂质体,能与靶细胞表面抗原或受体结合,从而对靶细胞具有分子水平上的识别能力。与游离药物、非特异抗体脂质体、单独单抗等相比,免疫脂质体有更好的选择性和更强的杀伤活性。在动物体内,免疫脂质体可使药物特异性分布在病灶部位,从而增强药物疗效、减轻不良反应,并且表面聚乙二醇化还增强了体内的循环时间。本文综述了用于修饰的不同种类抗体、抗体与免疫脂质体偶联方式,并总结了免疫脂质体在抗肿瘤药、基因治疗、活体成像技术以及在传染病、自身免疫和神经退行性疾病治疗方面的应用。  相似文献   
8.
目的: 以鼠抗人纤维蛋白D-二聚体单克隆抗体(DDmAb)为靶向装置,制备尿激酶(UK)的血栓靶向脂质体即尿激酶免疫脂质体,并在兔急性肺动脉栓塞模型上观察其早期溶栓效果。 方法: 新西兰大白兔40只,随机分为5组:TBS组(TBS缓冲液,阴性对照组)、UK组(15×104IU/kg UK,阳性对照组)、Lip组(5×104IU/kg UK的Lip-UK)、Ab组(5×104 IU/kg UK的Ab-Lip-UK)和2 Ab组(5×104 IU/kg UK但DDmAb用量为Ab组2倍,2 Ab-Lip-UK)。各组成功建立急性肺动脉栓塞模型后,分别以TBS缓冲液、UK、Lip-UK、Ab-Lip-UK和2 Ab-Lip-UK 各 30 mL经股静脉输入,进行兔体内溶栓实验,并观察右心室收缩压(RVSP)和右心室舒张压(RVDP)在1 h内随时间变化的情况。实验结束后,处死动物并取材,观察肺动脉内残留栓子数及心、肝、肾的肉眼和组织学变化。结果: TBS组RVSP在溶栓后1 h内无显著变化,UK组、Lip组、Ab组、2 Ab组RVSP分别于溶栓后30 min、40 min、30 min、20 min后显著下降。TBS组、UK组、Lip组、Ab组、2 Ab组肺内残留栓子数分别为:(4.0±0,2.4±0.9,3.1±0.6,2.4±0.9,1.9±0.6)个。各组肺均有不同程度的淤血、水肿表现。HE染色除UK组心、肝、肾有出血外,其余组未见出血。结论: 以2 Ab-Lip-UK这种具有双重靶向作用的药物进行溶栓治疗是肺动脉栓塞的一种理想溶栓方式,可缩短有效溶栓时间,疗效好且安全。  相似文献   
9.
Potential therapeutic applications of recently developed liposomes with a reduced affinity to the reticuloendothelial systems and a prolonged circulation time as targeting systems for lipophilic prodrugs were examined. In these studies, liposomes composed of phosphatidylcholine and cholesterol, additionally containing monosialoganglioside (GM1) or polyethylene glycol conjugated to phosphatidyl-ethanolamine (PEG-PE), were used. Three antitumor lipophilic prodrugs, N-trifluoroacetyl-adriamycin-14-valerate (AD32), araC-diphosphate-diglyceride (araCdPdG), and 3,5-o-dipalmitoyl-5-fluoro-2-deoxyuridine (dpFUdR), were used to examine the effect of lipophilic prodrug incorporation into long-circulating liposomes and immunoliposomes on their biodistribution in mouse. Biodistribution studies with antibody-free liposomes containing lipophilic prodrugs showed that the activities of GM1 or PEG2000-PE in prolonging the circulation time of liposomes appeared to be preserved in the presence of each of the three lipophilic prodrugs at a drug/lipid molar ratio of 3:97. The effect of lipophilic prodrug incorporation on target binding of immunoliposomes was then examined using a mouse model. Incorporation of AD32 or dpFUdR into immunoliposomes, directed to the normal endothelium, did not affect the targetability of immunoliposomes, suggesting a potential effectiveness of these lipophilic prodrug-containing immunoliposomes in therapy for lung tumors. On the contrary, incorporation of araCdPdG resulted in significantly reduced target binding of immunoliposomes by yet unknown mechanism(s).  相似文献   
10.
阿苯达唑免疫脂质体的制备   总被引:9,自引:0,他引:9  
目的制备阿苯达唑免疫脂质体,提高阿苯达唑治疗包虫病的靶向特异性.方法采用注入-pH梯度法制备了脂质体;接着进一步采用戊二醛法将单克隆抗体与脂质体偶联制备免疫脂质体.结果脂质体的包封率为(64.02±3.10)%,粒径20~80 nm;用ELISA法检测了免疫脂质体抗体效价,其活性仍保留近80%.结论阿苯达唑免疫脂质体可成为抗细粒棘球蚴病特异靶向药物.  相似文献   
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